Genetic counseling: Fetal Hydantoin Syndrome
Fetal Hydantoin Syndrome Etiology *Prenatal hydantoin (dilantin, phenytoin) exposure History/Epidemiology *Phenytoin= anticonvulsant first introduced in1938. *Teratogenic effects were first recognized in 1964. *Numerous studies have demonstrated increased risk for congenital defects, both major and minor. *Study conducted from 1985-1992 **332 newborns exposed to phenytoin (hydantoin, dilantin) during the 1st trimester **A total of 15 (4.5%) had major birth defects, including: ***Cardiovascular ***Spina bifida ***Hypospadias Clinical Features *Craniofacies: **Broad nasal bridge, wide anterior fontanelle, low hairline, broad alveolar ridge, short neck, hypertelorism, microcephaly, cleft lip/palate, low set ears, epicanthal folds, ptosis, coloboma, coarse scalp hair. *Limbs: **Small or absent nails, hypoplasia of distal phalanges, altered palmar crease, digital thumb, dislocated hip *Growth: **Mild to moderate growth deficiency, usually prenatal in onset *Performance: **Occasional borderline to mild mental deficiency. Performance in childhood is usually better than that predicted in infancy *Cardiovascular (occasional abnormalities): **Aortic valvular stenosis, coarctation of aorta, PDA, septal defects *GI (occasional abnormalities): **Pyloric stenosis, duodenal atresia, anal atresia *Other (occasional): **Small nipples that are widely spaced, umbilical and inguinal hernia. Risks *Risks of delivering a child with congenital defects is 2-3x greater for women taking dilantin than for the general population. **Increased risk could be caused by epilepsy, the drugs, or a combination of the two. It is thought that the drugs are the causative factor. *Risks of child having full syndrome is about 10% and the risk for having some of the effects of the disorder is an additional 33% *Some reports have shown that phenytoin is a transplacental carcinogen. Tumors were reported to occur after in utero exposure to phenytoin in a few cases. *Phenytoin may induce folic acid deficiency in the epileptic patient by impairing GI absorption or by increasing hepatic metabolism. Therefore, the risk for having a baby with a spinal abnormality is increased. *Some risk of early hemorrhagic disease of the newborn. Occurs during the 1st 24 hours after birth and can be fatal. Exact mechanism: unknown. Drug is thought to deplete already low levels of fetal vitamin K therefore suppressing the vitamin K-dependent coagulation factors II, VII, IX, and X. Proposed treatment regimen: taking oral vitamin K during last 2 months of pregnancy, C section if difficult labor or trauma is suspected, administering intravenous vitamin K to the newborn in the delivery room (this regimen hasn't been tested in clinical controlled trials, but are logical). *Risk of not taking phenytoin: pregnant patient can have seizures and can cause the baby to have fetal hypoxia. Breast Feeding *Phenytoin is excreted into breast milk. Milk:plasma ratios range from 0.18 to 0.54. *Little risk to the infant if maternal levels are kept in the therapeutic range *Drowsiness and decreased sucking were observed in one infant, no other adverse effects have been reported. *The American Academy of Pediatrics considers phenytoin to be compatible with breast feeding. References *www.reprotox.org *Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th edition. Baltimore: Williams & Wilkins. *Jones KL. Smith's Recognizable Patterns of Human Malformations. 5th edition. W.B. Saunders Company: Philadelphia. 1997. Notes The information in this outline was last updated in 2002. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.